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mNSCLC - L1 - PDL1 positive, pembrolizumab alone , meta-analysis of study results

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

deaths (OS) 0.83 [0.64, 1.09]< 173%3 studies (3/-)91.2 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.72 [0.57, 0.92]< 167%2 studies (2/-)99.5 %some concernnot evaluable moderateimportant-
PFS (extension) 0.73 [0.35, 1.51]< 196%2 studies (2/-)80.1 %some concernnot evaluable moderateimportant-
progression or deaths (PFS) 0.85 [0.58, 1.24]< 191%3 studies (3/-)80.3 %some concernnot evaluable moderateimportant-
objective responses (ORR) 1.24 [0.85, 1.82]> 173%3 studies (3/-)86.6 %some concernnot evaluable moderatenon important-
objective responses (ORR) (extension) 1.35 [0.75, 2.44]> 180%2 studies (2/-)84.1 %some concernnot evaluable moderatenon important-

safety endpoints 00

STRAE (any grade) 1.05 [0.60, 1.82]< 10%1 study (1/-)43.5 %NAnot evaluable non important-
STRAE (grade 3-4) 0.97 [0.55, 1.72]< 10%1 study (1/-)54.4 %NAnot evaluable non important-
TRAE (any grade) 0.22 [0.14, 0.34]< 144%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.30 [0.24, 0.38]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.81 [0.39, 1.66]< 10%2 studies (2/-)71.9 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.88 [0.62, 1.24]< 10%2 studies (2/-)76.5 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (grade 3-4) 1.05 [0.71, 1.55]< 10%2 studies (2/-)41.1 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 3.88 [0.17, 86.15]< 10%1 study (1/-)19.9 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 0.07 [0.00, 1.21]< 10%1 study (1/-)96.5 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.06 [0.03, 0.12]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
Arthralgia TRAE (grade 3-4) 0.97 [0.02, 48.81]< 10%1 study (1/-)50.7 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.29 [0.08, 1.05]< 10%1 study (1/-)97.0 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 0.49 [0.02, 14.58]< 10%1 study (1/-)65.9 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 3.90 [0.65, 23.43]< 10%2 studies (2/-)6.9 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.97 [0.06, 15.56]< 10%2 studies (2/-)50.8 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.44 [0.16, 1.24]< 10%2 studies (2/-)93.8 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 1.95 [0.07, 58.69]< 10%1 study (1/-)35.2 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 3.57 [0.98, 13.00]< 10%2 studies (2/-)2.7 %some concernnot evaluable moderatenon important-
Dysgeusia TRAE (grade 3-4) 0.97 [0.02, 49.41]< 10%1 study (1/-)50.5 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.37 [0.13, 1.04]< 10%2 studies (2/-)97.0 %some concernnot evaluable moderatenon important-
Hepatitis TRAE (grade 3-4) 13.68 [0.77, 241.54]< 10%1 study (1/-)3.9 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.44 [0.11, 18.83]< 10%2 studies (2/-)39.1 %some concernnot evaluable moderatenon important-
Hypophysitis TRAE (grade 3-4) 3.62 [0.38, 34.25]< 10%2 studies (2/-)13.3 %some concernnot evaluable moderatenon important-
Hypothyroidism TRAE (grade 3-4) 1.44 [0.11, 18.83]< 10%2 studies (2/-)39.1 %some concernnot evaluable moderatenon important-
Increase AST TRAE (grade 3-4) 1.94 [0.35, 10.63]< 10%1 study (1/-)22.3 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 1.75 [0.58, 5.26]< 10%1 study (1/-)15.9 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.24 [0.04, 1.55]< 10%2 studies (2/-)93.2 %some concernnot evaluable moderatenon important-
Leucopenia TRAE (grade 3-4) 0.05 [0.00, 0.82]< 10%1 study (1/-)98.1 %NAnot evaluable non important-
Myalgia TRAE (grade 3-4) 1.94 [0.06, 57.80]< 10%1 study (1/-)35.4 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 1.94 [0.06, 57.80]< 10%1 study (1/-)35.4 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 0.97 [0.02, 49.41]< 10%1 study (1/-)50.5 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.10 [0.01, 0.82]< 10%2 studies (2/-)98.4 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 1.94 [0.18, 21.52]< 10%2 studies (2/-)29.5 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 0.02 [0.00, 0.10]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
Pancreatitis TRAE (grade 3-4) 1.44 [0.11, 18.87]< 10%2 studies (2/-)39.0 %some concernnot evaluable moderatenon important-
Peripheral neuropathy TRAE (grade 3-4) 0.10 [0.01, 1.76]< 10%1 study (1/-)94.1 %NAnot evaluable non important-
Peripheral sensory neuropathy TRAE (grade 3-4) 0.08 [0.00, 1.43]< 10%1 study (1/-)95.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 9.73 [1.92, 49.42]< 116%2 studies (2/-)0.3 %some concernnot evaluable moderatenon important-
Pruritus TRAE (grade 3-4) 3.88 [0.17, 86.15]< 10%1 study (1/-)19.9 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 0.97 [0.02, 49.41]< 10%1 study (1/-)50.5 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 5.82 [0.29, 116.52]< 10%1 study (1/-)12.7 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 11.23 [2.11, 59.83]< 10%2 studies (2/-)0.2 %some concernnot evaluable moderatenon important-
Stomatitis TRAE (grade 3-4) 0.41 [0.04, 4.70]< 10%2 studies (2/-)76.1 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 0.08 [0.02, 0.43]< 10%2 studies (2/-)99.8 %some concernnot evaluable moderatenon important-
Thyroiditis TRAE (grade 3-4) 0.97 [0.06, 15.56]< 10%2 studies (2/-)50.8 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.52 [0.07, 4.14]< 10%2 studies (2/-)72.9 %some concernnot evaluable moderatenon important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.